Organic &Biomolecular Chemistry

PAPER

Cite this: Org. Biomol. Chem., 2014,12, 2969

Received 1st January 2014,Accepted 5th March 2014

DOI: 10.1039/c4ob00002a

www.rsc.org/obc

KOAc-promoted alkynylation of α-C–H bondsof ethers with alkynyl bromides undertransition-metal-free conditions†

Jiajun Zhang,a Pinhua Li*a and Lei Wang*a,b

A novel KOAc-promoted α-position C–H activation and alkynylation of ethers with alkynyl bromides to

2-alkynyl ethers has been developed under transition-metal-free and simple reaction conditions. In

addition, this methodology can also be extended to the vinylation of ethers with vinyl bromides in excel-

lent regio- and stereo-selectivity. A wide range of direct C(sp)–C(sp3) and C(sp2)–C(sp3) bonds has been

formed through this protocol, which offers a new and alternative route.

Introduction

The transition-metal catalyzed direct conversion of C–H bondsinto C–C bonds has been one of the most attractive subjects incontemporary organic chemistry. In the past few decades, sig-nificant efforts have been made on C–H activation andfunctionalization, and various high efficiency and versatile pro-tocols have been explored.1 Despite remarkable advancesachieved in this field, critical issues such as stoichiometricamounts of metal waste and the presence of metal impuritiesin the final product may restrict their practical applicability.Hence, the green and economical platform for mediatingorganic transformations is demanded. Recently, Itami, Kwong/Lei, Shi, and Shirakawa/Hayashi have reported the astonishingresults on the construction of C–C bonds from unactivated aro-matic rings by direct C–H activation without the aid of tran-sition metals,2 and these breakthroughs might bring in a newera of organic synthesis.3 From the viewpoint of green chem-istry, the organic reactions carried out under transition-metal-free conditions, avoiding metal contamination in the final pro-ducts, have been paid much attention in modern organic syn-thesis, especially in the pharmaceutical industry. In the pasttwo years, a variety of protocols for the direct C–H bond acti-vation and functionalization in the absence of transitionmetals have been established.4 The representative systems are

KOtBu,2b,c,4b,k,r–v and NaOtBu2d in the presence of an effectiveligand except one example.4k

Substituted tetrahydrofurans are not only valuable buildingblocks in organic synthesis, but also are ubiquitous motifspresent in biological, pharmaceutical and natural products.5

In general, they are usually accessible through the α-C(sp3)–Hactivation/functionalization of tetrahydrofuran (THF),6 such asNi-catalyzed arylation of THF,7 Fe(II)-catalyzed CDC reaction ofTHF with malonates,8 Cu- and Ir-catalyzed carbenoid insertionof ethyl diazoacetate into α-C–H of THF,9 Cr-promoted reactionof alcohols with THF to 2-tetrahydrofuranyl ethers,10 AIBN-mediated alkenylation of THF with vinyl triflones,11 TBHP-pro-moted reaction of phenylacetylene with THF to allylic ether,12

and BEt3- and Me2Zn-mediated addition of THF with alde-hydes and aldimines under air, respectively.13 2-Alkynyl cyclicethers, potential structural motifs of bioactive molecules andmaterials, have been successfully prepared by region-specificα-position alkynylation of cyclic ethers.14–16 In 1988, Leyconverted 2-benzenesulphonyl cyclic ethers to 2-alkynyl tetra-hydrofuran by treatment with the corresponding organozincagents (Scheme 1).14 In 1996, Fuchs developed a syntheticstrategy to produce 2-alkynyl cyclic ethers through the alkyny-lation of α-position C–H bonds in cyclic ethers with acetylenictriflones under peroxide or AIBN or UV-irradiation.15 Mostrecently, Anderson reported an efficient Pd-catalyzed synthesisof 2-alkynyl oxacycles from their cyclic and acycliccarbonates.16

Encouraged by the above transformations, and in continu-ation of our and others interest in transformation of C(sp3)–H bonds into C(sp3)–C bonds,17 we conceived that alkynylationof α-position C–H bonds of ethers with alkynyl bromideswithout the assistance of a transition metal may be possible.Herein, we wish to report an efficient reaction of alkynyl bro-mides with cyclic ethers for direct C(sp)–C(sp3) bond for-

†Electronic supplementary information (ESI) available: Detailed procedures,analytical data, and 1H, 13C NMR and HRMS spectra of all intermediates andproducts or other electronic format. CCDC 955471. For ESI and crystallographicdata in CIF or other electronic format see DOI: 10.1039/c4ob00002a

aDepartment of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000,

P R China. E-mail: leiwang@chnu.edu.cn; Fax: +86-561-309-0518;

Tel: +86-561-380-2069bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic

Chemistry, Chinese Academy of Sciences, Shanghai 200032, P R China

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mation through KOAc-promoted α-position C–H activation andalkynylation of ethers under transition-metal-free and simplereaction conditions (Scheme 1). Moreover, this methodologycan also be extended to the vinylation of α-C–H bonds ofethers with vinyl bromides with excellent regio- and stereo-selectivity.

Results and discussion

In the initial investigation of the reaction of alkynyl bromidesto ethers, phenylethynyl bromide (1a) and tetrahydrofuran(THF, 2a) were chosen as model substrates. When the modelreaction was carried out in the presence of Na2CO3 at 150 °Cin a sealed pressure tube for 12 h without an additionalsolvent, a direct alkynylation product (3a) of THF via α-posi-tion C–H bond activation was isolated in 59% yield (Table 1,entry 1).

Encouraged by this positive result, further investigation onthe addition of a transition metal to the reaction was exam-ined. Unfortunately, transition metals, such as Pd(OAc)2, CuI,and AgBF4, completely shut down the reaction (Table 1, entries2–4). To improve the desired product yield, detailed investi-gation on the effect of a base on the reaction was examined. Toour delight, KOAc exhibited the highest reactivity to the reac-tion among the tested bases, providing 93% yield of 3a(Table 1, entry 5). Other bases, such as NaOAc, NaHCO3,(NH4)2CO3, K2CO3, KHCO3, Cs2CO3, K3PO4, NaF, and KF, wereinferior and generated 3a in 13–74% yields (Table 1, entries6–14). However, when the reaction was performed in the pres-ence of LiOtBu, NaOtBu, KOtBu, KOH, NaOH, Et3N, DBU, orDABCO as a base, no 3a was detected and starting materialswere unchanged and recovered (Table 1, entries 15–22).However, only 32% yield of 3a was generated in the absence ofany base, catalyst and additive (Table 1, entry 23).

To further examine the effect of ligand for the improvementof model reaction, L-proline, N,N,N′,N′-tetramethylethylenedi-amine (TMEDA), 1,10-phenanthroline (1,10-Phen) and 2,2′-

bipyridine (Bipy), 8-hydroxyquinoline (8-HQ), and 1,1′-bis-(diphenylphosphino)ferrocene (Dppf) were added to theKOtBu, NaOtBu or LiOtBu system which promoted the reaction,but failed (Table S1, ESI,† entries 1–18).

With respect to the base loading, 2 equiv. of KOAc wasfound to be optimal. When the model reaction was carried outin the presence of KOAc, a significant reaction temperatureeffect was observed. When the reaction was performed at lessthan 100 °C, poor yields of 3a were obtained. The optimaltemperature was found to be 150 °C (Table 2, entries 1–7).

Scheme 1 Preparation of 2-alkynyl tetrahydrofurans.

Table 1 Effect of a base and a catalyst on the reactiona

Entry Base Catalyst Yieldb (%)

1 Na2CO3 — 592 Na2CO3 Pd(OAc)2 NR3 Na2CO3 CuI NR4 Na2CO3 AgBF4 NR5 KOAc — 936 NaOAc — 747 NaHCO3 — 528 (NH4)2CO3 — 479 K2CO3 — 4310 KHCO3 — 4211 Cs2CO3 — 3212 K3PO4 — 2113 NaF — 1814 KF — 1315 LiOtBu — NR16 NaOtBu — NR17 KOtBu — NR18 KOH — NR19 NaOH — NR20 Et3N — NR21 DBU — NR22 DABCO — NR23 — — 32

a Reaction conditions: 1a (0.30 mmol), 2a (2.0 mL, excess, as well assolvent), catalyst (5.0 mol%) if needed, base (0.60 mmol), at 150 °C for12 h. b Isolated yield.

Table 2 Effect of temperature on the model reactiona

Entry Temp. (°C) Yieldb (%)

1 80 222 100 403 120 644 140 805 150 936 160 937 170 90

a Reaction conditions: 1a (0.30 mmol), 2a (2.0 mL, excess), KOAc(0.60 mmol) at the temperature indicated in this table for 12 h.b Isolated yield.

Paper Organic & Biomolecular Chemistry

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The final investigation revealed that an additional solvent,such as DMF, DMA, NMP, DMSO, CH3CN, HOAc, CH3CH2OH,CH3NO2, DCE (1,2-dichloroethane) or toluene has a great nega-tive effect on the reaction (Table 3, entries 1–10). The opti-mized reaction conditions for the model reaction were in thepresence of KOAc at 150 °C for 12 h.

With the optimized reaction conditions in our hand, avariety of substituted phenylethynyl bromides were selected tocouple with tetrahydrofuran for the synthesis of 2-alkynyl-tetra-hydrofurans (Scheme 2). Pleasingly, phenylethynyl bromideswith electron-donating groups, such as MeO, Me, n-Pr andt-Bu, at the para-, meta-, or ortho-positions of phenyl ringsunderwent the reaction smoothly with THF (2a), generatingthe corresponding products 3b–g in good yields (75–86%).Meanwhile, phenylethynyl bromides with electron-withdraw-ing groups, such as CH3CO and F3C, also proceeded well withTHF to afford the desired products 3k and 3l in 74% and 76%yields, respectively. Moreover, substrates with halogen substi-tuents such as F, Cl, and Br could be well transformed into thetarget products 3h–j in good yields. In addition, metal- andortho-substituents could also be well tolerated in this reaction(3m and 3n).

Considering the importance of direct functionalization ofdifferent ethers, other simple ethers were also tested to couplewith phenylethynyl bromide derivatives under optimized con-ditions (Scheme 3). 2-Methyl tetrahydrofuran was first testedto couple with different phenylethynyl bromides. We were sur-prised to find that reaction selectively occurred at the methynegroup, affording the corresponding products in good yieldsand excellent regio-selectivity (3o–q). Tetrahydropyran and 1,4-dioxane were also found to react smoothly with phenylethynylbromide or (4-tert-butylphenyl)ethynyl bromide to generate thealkynylation products 3r–t in moderate yields. Moreover, whenbenzene fused tetrahydrofurans, such as 2,3-dihydrobenzo-furan and 1,3-dihydroisobenzofuran, were employed, theanticipated products, 3u and 3v, were obtained in 55% and46% yields, respectively. Notably, this methodology could also

Scheme 2 KOAc-promoted direct alkynylation of tetrahydrofuranunder transition-metal free conditions. Reaction conditions: 1(0.30 mmol), 2a (2.0 mL, excess, as well as a solvent), KOAc(0.60 mmol), at 150 °C for 12 h; isolated product yields afterchromatography.

Scheme 3 KOAc-promoted direct alkynylation of other simple ethersunder transition-metal free conditions. Reaction conditions: 1(0.30 mmol), 2 (2.0 mL, excess, as well as solvent), KOAc (0.60 mmol), at150 °C for 12 h; isolated product yields after chromatography.

Table 3 Effect of solvent on the model reactiona

Entry Solvent/temp. (°C) Yieldb (%)

1 DMF/150 NR2 DMA/150 73 NMP/150 NR4 DMSO/150 NR5 CH3CN/100 56 HOAc/100 NR7 CH3CH2OH/100 NR8 CH3NO2/100 NR9 DCE/100 1310 Toluene/150 Trace

a Reaction conditions: 1a (0.30 mmol), 2a (2.0 mL, excess), KOAc(0.60 mmol), solvent (2.0 mL) at the temperature indicated in thistable for 12 h. b Isolated yield.

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be extended to chain-like ethers. 1,2-Dimethoxyethane reactedsmoothly with 1a to afford the corresponding product 3w inmoderate yield, along with excellent regio-selectivity. Inaddition, the substrate scope of alkyne bromide was extendedto aliphatic alkyne bromides, such as 1-(bromoethynyl)cyclo-hexanol and 1-bromohept-1-yne, and satisfactory results wereachieved (Scheme 3, 3x and 3y).

Additionally, the regio-selectivity of direct alkynylation of1,3-dioxolane with phenylethynyl bromide was investigatedunder the present reaction conditions. The results showed that82% total yield of 3x and 3x′ was isolated with a ratio of 65 : 17(Scheme 4), which indicated that the stability of free radicalsplays an important role in this reaction.

Later on, the vinylation of α-C–H bonds of ethers with vinylbromides in the presence of KOAc was also examined, and theresults are shown in Scheme 4. When a mixture of cis- andtrans-(2-bromovinyl)benzene (1 : 5) reacted with tetrahydro-furan and 2-methyltetrahydrofuran to generate the corres-ponding products 5a and 5b in moderate yields respectivelywith excellent regio- and stereo-selectivity. The prepared (Z)-2-bromovinyl phenyl ethers,18a 4b and 4c, reacted with THFunder the optimized reaction conditions, providing the corres-ponding exclusive (Z)-type products 5c and 5d (Scheme 5) inmoderate yields. It also provides an effective and alternative

route to vinyl cycloethers with excellent regio- and stereo-selec-tivity.12,15b,19 Moreover, the representative structure of 5d wasconfirmed by X-ray single crystal analysis.20

To investigate the reaction mechanism, the related experi-ments were performed. When a radical scavenger, 2,2,6,6-tetra-methylpiperidyl-1-oxyl (TEMPO, 1.5 equiv.), was added to thestandard reaction system, the reaction was completely shutdown, along with formation of a radical-trapping product,detected by GC/MS (see the ESI† for details), suggesting that acarbon-centered radical of THF is probably involved in thisreaction. In addition, when reaction was carried out understrictly anhydrous and anaerobic conditions, no product wasdetected and only starting materials were recovered, and theadded peroxide (such as H2O2) could improve the reaction sig-nificantly. Based on the experimental results, a proposedmechanism of KOAc-promoted direct C–H alkynylation ofsimple ethers is depicted in Scheme 6. Firstly, a tetrahydro-furan radical (I) was generated in the presence of smallamounts of peroxide in THF (2a). Subsequently, a radicaladdition of the obtained (I) to phenylethynyl bromide (1a)occurred smoothly to afford a bromovinyl radical (II), whichgenerated a bromine free radical and the final product (3a)through a bromine radical elimination process. Finally, thebromine radical abstracted a hydrogen radical from THF (2a)to generate intermediate (I) with the aid of a suitable base(KOAc).

Conclusion

In conclusion, we have established a novel Csp–Csp3 bond for-mation through KOAc-promoted direct C–H alkynylation ofsimple ethers under transition-metal free and simple reactionconditions.21 Different substituted phenylethynyl bromidesand common simple ethers could be cross-coupled smoothlyto afford the corresponding products in good to excellent

Scheme 4 Regio-selectivity investigation of direct alkynylation of 1,3-dioxolane with phenylethynyl bromide.

Scheme 5 Direct vinylation of α-C–H bonds of ethers with vinylbromides.

Scheme 6 Proposed reaction mechanism.

Paper Organic & Biomolecular Chemistry

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yields. In addition, this methodology can also be extended tothe direct C–H vinylation of ethers with excellent regio- andstereo-selectivity. A wide range of direct Csp–Csp3 and Csp2–Csp3 bonds could be constructed through this protocol,offering a brand new and alternative route for the synthesis of2-alkynyl- and 2-alkenyl ethers.22 Further detailed investigationof the reaction mechanism and application of this kind ofstrategy is underway in our laboratory.

Experimental section

All the bromoalkynes18b and bromo alkenes,18a such as (Z)-2-bromovinyl phenyl ethers, 4b and 4c, as starting materialswere prepared according to the reported procedure in the lit-erature.18a,b All the chemicals and solvents were purchasedfrom commercial suppliers and used without further purifi-cation. All reactions were carried out under air. 1H NMR and13C NMR spectra were measured on a Bruker Avance NMRspectrometer (400 MHz or 100 MHz, respectively) in CDCl3 asa solvent and recorded in ppm relative to the internal tetra-methylsilane standard. 1H NMR data are reported as follows: δ,chemical shift; coupling constants ( J values are given in hertz,Hz) and integration. Abbreviations to denote the multiplicityof a particular signal were s (singlet), d (doublet), t (triplet),q (quartet), m (multiplet), and br (broad singlet). High resolu-tion mass spectroscopy data of the products were collected ona Waters Micromass GCT instrument using EI (70 eV) or anAgilent Technologies 6540 UHD Accurate-Mass Q-TOF LC/MSusing ESI.

A typical procedure for KOAc-promoted alkynylation of α-C–Hbonds of ethers with alkynyl bromides

Under an air atmosphere, a 10 mL oven-dried sealable reactionvessel equipped with a magnetic stir bar charged with phenyl-ethynyl bromide (1a, 54.3 mg, 0.30 mmol), KOAc (59 mg,0.60 mmol) and tetrahydrofuran (THF, 2a, 2.0 mL, excess, aswell as solvent) was added to the sealed vessel in one portion.The rubber septum was then replaced by a Teflon-coated screwcap, and the reaction vessel was placed in an oil bath at 150 °Cfor 12 h. After the reaction was completed, it was cooled toroom temperature and diluted with ethyl acetate. The resultingsolution was directly filtered through a pad of silica gel using asintered glass funnel, and concentrated under reducedpressure. The residue was purified by flash chromatography onsilica gel (eluant: petroleum ether–ethyl acetate = 10 : 1 to25 : 1, v/v) to obtain the desired pure product, 2-(phenyl-ethynyl)tetrahydrofuran (3a).

2-(Phenylethynyl)tetrahydrofuran (3a).16 Colorless oil. 1HNMR (400 MHz, CDCl3) δ: 7.45–7.43 (m, 2H), 7.30–7.29 (m,3H), 4.83–4.80 (m, 1H), 4.05–3.99 (m, 1H), 3.89–3.83 (m, 1H),2.26–2.19 (m, 1H), 2.13–2.04 (m, 2H), 1.98–1.92 (m, 1H); 13CNMR (100 MHz, CDCl3) δ: 131.70, 128.24, 128.21, 122.83,

89.11, 84.46, 68.60, 67.92, 33.42, 25.50. HRMS (EI) ([M]+) CalcdFor C12H12O: 172.0888, found: 172.0883.

2-((4-Methoxyphenyl)ethynyl)tetrahydrofuran (3b). Colorlessoil. 1H NMR (400 MHz, CDCl3) δ: 7.37 (d, J = 8.4 Hz, 2H), 6.83(d, J = 8.8 Hz, 2H), 4.82–4.79 (m, 1H), 4.04–3.99 (m, 1H),3.88–3.85 (m, 1H), 3.80 (s, 3H), 2.25–2.19 (m, 1H), 2.13–2.03(m, 2H), 1.99–1.92 (m, 1H); 13C NMR (100 MHz, CDCl3) δ:159.55, 133.16, 114.90, 113.82, 87.59, 84.37, 68.69, 67.88,55.25, 33.45, 25.51. HRMS (EI) ([M]+) Calcd For C13H14O2:202.0994, found: 202.0990.

2-(p-Tolylethynyl)tetrahydrofuran (3c). Colorless oil. 1HNMR (400 MHz, CDCl3) δ: 7.33 (d, J = 8.0 Hz, 2H), 7.11 (d, J =7.6 Hz, 2H), 4.83–4.80 (m, 1H), 4.05–3.99 (m, 1H), 3.89–3.84(m, 1H), 2.34 (s, 3H), 2.26–2.20 (m, 1H), 2.13–2.04 (m, 2H),1.99–1.92 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 138.33,131.61, 128.97, 119.71, 88.31, 84.59, 68.66, 67.91, 33.44, 25.51,21.46. HRMS (ESI) ([M + H]+) Calcd For C13H15O: 187.1123,found: 187.1123.

2-((4-n-Propylphenyl)ethynyl)tetrahydrofuran (3d). Colorlessoil. 1H NMR (400 MHz, CDCl3) δ: 7.35 (d, J = 8.0 Hz, 2H), 7.11(d, J = 8.0 Hz, 2H), 4.83–4.80 (m, 1H), 4.05–3.99 (m, 1H),3.89–3.84 (m, 1H), 2.58 (t, J = 7.6 Hz, 2H), 2.26–2.19 (m, 1H),2.12–2.06 (m, 2H), 1.99–1.92 (m, 1H), 1.67–1.60 (m, 2H), 0.94(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 143.08,131.59, 128.36, 119.98, 88.35, 84.62, 68.66, 67.87, 37.90, 33.45,25.48, 24.29, 13.71. HRMS (ESI) ([M + H]+) Calcd For C15H19O:215.1436, found: 215.1441.

2-((4-(tert-Butyl)phenyl)ethynyl)tetrahydrofuran (3e). Color-less oil. 1H NMR (400 MHz, CDCl3) δ: 7.38 (d, J = 8.4 Hz, 2H),7.32 (d, J = 8.4 Hz, 2H), 4.83–4.80 (m, 1H), 4.05–4.00 (m, 1H),3.89–3.84 (m, 1H), 2.26–2.19 (m, 1H), 2.13–2.04 (m, 2H),1.99–1.92 (m, 1H), 1.31 (s, 9H); 13C NMR (100 MHz, CDCl3) δ:151.44, 131.42, 125.20, 119.80, 88.36, 84.56, 68.67, 67.87,34.72, 33.47, 31.17, 25.48. HRMS (ESI) ([M + H]+) calcd forC16H21O: 229.1592, found: 229.1588.

2-(m-Tolylethynyl)tetrahydrofuran (3f). Colorless oil. 1HNMR (400 MHz, CDCl3) δ: 7.27–7.24 (m, 2H), 7.21–7.17 (m,1H), 7.13–7.11 (m, 1H), 4.84–4.81 (m, 1H), 4.05–4.00 (m, 1H),3.90–3.84 (m, 1H), 2.32 (s, 3H), 2.26–2.20 (m, 1H), 2.14–2.04(m, 2H), 2.01–1.93 (m, 1H); 13C NMR (100 MHz, CDCl3) δ:

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137.86, 132.31, 129.12, 128.76, 128.10, 122.61, 88.71, 84.61,68.62, 67.90, 33.44, 25.48, 21.18. HRMS (ESI) ([M + H]+) calcdfor C13H15O: 187.1123, found: 187.1123.

2-(o-Tolylethynyl)tetrahydrofuran (3g). Colorless oil. 1HNMR (400 MHz, CDCl3) δ: 7.41 (d, J = 7.6 Hz, 1H), 7.22–7.18(m, 2H), 7.15–7.11 (m, 1H), 4.89–4.86 (m, 1H), 4.06–4.01 (m,1H), 3.92–3.86 (m, 1H), 2.43 (s, 3H), 2.28–2.22 (m, 1H),2.16–2.07 (m, 2H), 2.02–1.93 (m, 1H); 13C NMR (100 MHz,CDCl3) δ: 140.21, 132.00, 129.34, 128.27, 125.45, 122.56, 93.07,83.34, 68.72, 67.83, 33.59, 25.41, 20.65. HRMS (EI) ([M]+) calcdFor C13H14O: 186.1045, found: 186.1044.

2-((4-Fluorophenyl)ethynyl)tetrahydrofuran (3h). Colorlessoil. 1H NMR (400 MHz, CDCl3) δ: 7.42–7.39 (m, 2H), 7.00–6.96(m, 2H), 4.80–4.77 (m, 1H), 4.03–3.97 (m, 1H), 3.88–3.82 (m,1H), 2.25–2.18 (m, 1H), 2.10–2.05 (m, 2H), 1.98–1.91 (m, 1H);13C NMR (100 MHz, CDCl3) δ: 162.46 (d, JCF = 247.8 Hz),133.58 (d, JCF = 8.3 Hz), 118.90 (d, JCF = 3.5 Hz), 115.45 (d, JCF =21.9 Hz), 88.78, 83.39, 68.51, 67.93, 33.36, 25.49. HRMS (EI)([M]+) calcd For C12H11FO: 190.0794, found: 190.0789.

2-((4-Chlorophenyl)ethynyl)tetrahydrofuran (3i). Colorlessoil. 1H NMR (400 MHz, CDCl3) δ: 7.36 (d, J = 8.4 Hz, 2H), 7.27(d, J = 8.4 Hz, 2H), 4.81–4.78 (m, 1H), 4.03–3.98 (m, 1H),3.89–3.83 (m, 1H), 2.26–2.20 (m, 1H), 2.12–2.03 (m, 2H),2.00–1.91 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 134.28,132.93, 128.54, 121.32, 90.10, 83.35, 68.51, 67.99, 33.34, 25.50.HRMS (EI) ([M]+) calcd For C12H11ClO: 206.0498, found:206.0501.

2-((4-Bromophenyl)ethynyl)tetrahydrofuran (3j). Colorlessoil. 1H NMR (400 MHz, CDCl3) δ: 7.43 (d, J = 8.4 Hz, 2H), 7.29(d, J = 8.4 Hz, 2H), 4.81–4.78 (m, 1H), 4.04–3.98 (m, 1H),3.89–3.84 (m, 1H), 2.27–2.20 (m, 1H), 2.13–2.05 (m, 2H),2.00–1.93 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 133.15,131.48, 122.49, 121.79, 90.30, 83.41, 68.52, 68.00, 33.32, 25.50.HRMS (ESI) ([M + H]+) calcd For C12H12BrO: 251.0072, found:251.0072.

2-((4-Acetyphenyl)ethynyl)tetrahydrofuran (3k). Colorlessoil. 1H NMR (400 MHz, CDCl3) δ: 7.88 (d, J = 8.4 Hz, 2H), 7.49(d, J = 8.0 Hz, 2H), 4.83–4.80 (m, 1H), 4.03–3.98 (m, 1H),3.89–3.83 (m, 1H), 2.58 (s, 3H), 2.28–2.20 (m, 1H), 2.13–2.04(m, 2H), 1.99–1.91 (m, 1H); 13C NMR (100 MHz, CDCl3) δ:

197.25, 136.29, 131.80, 128.12, 127.70, 92.55, 83.68, 68.48,68.06, 33.30, 26.55, 25.51. HRMS (ESI) ([M + H]+) calcd forC14H15O2: 215.1072, found: 215.1071.

2-((4-(Trifluoromethyl)phenyl)ethynyl)tetrahydrofuran (3l).Colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.57–7.55 (m, 2H),7.54–7.52 (m, 2H), 4.84–4.81 (m, 1H), 4.05–3.99 (m, 1H),3.90–3.85 (m, 1H), 2.29–2.22 (m, 1H), 2.14–2.05 (m, 2H),2.01–1.95 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 131.92,129.99 (q, JCF = 32.4 Hz), 126.64, 125.14 (q, JCF = 3.8 Hz),123.88 (q, JCF = 270.4 Hz), 91.66, 83.12, 68.42, 68.07, 33.29,25.50. HRMS (EI) ([M]+) calcd for C13H11F3O: 240.0762, found:240.0763.

2-((3-Fluorophenyl)ethynyl)tetrahydrofuran (3m). Colorlessoil. 1H NMR (400 MHz, CDCl3) δ: 7.29–7.25 (m, 1H), 7.24–7.20(m, 1H), 7.13 (d, J = 9.6 Hz, 1H), 7.04–7.00 (m, 1H), 4.83–4.80(m, 1H), 4.04–3.99 (m, 1H), 3.90–3.85 (m, 1H), 2.27–2.21 (m,1H), 2.14–2.06 (m, 2H), 2.00–1.94 (m, 1H); 13C NMR (100 MHz,CDCl3) δ: 162.28 (d, JCF = 244.8 Hz), 129.77 (d, JCF = 8.6 Hz),127.58 (d, JCF = 3.1 Hz), 124.66 (d, JCF = 9.5 Hz), 118.50 (d, JCF =22.7 Hz), 115.60 (d, JCF = 21.0 Hz), 90.09, 83.23 (d, JCF = 3.4Hz), 68.46, 68.01, 33.33, 25.49. HRMS (EI) ([M]+) calcd forC12H11FO: 190.0794, found: 190.0793.

2-((2-Fluorophenyl)ethynyl)tetrahydrofuran (3n). Colorlessoil. 1H NMR (400 MHz, CDCl3) δ: 7.45–7.41 (m, 1H), 7.31–7.26(m, 1H), 7.10–7.03 (m, 2H), 4.87–4.84 (m, 1H), 4.05–4.00 (m,1H), 3.90–3.85 (m, 1H), 2.28–2.22 (m, 1H), 2.16–2.08 (m, 2H),2.00–1.94 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 162.77 (d, JCF= 250.1 Hz), 133.62 (d, JCF = 1.3 Hz), 129.97 (d, JCF = 7.9 Hz),123.81 (d, JCF = 3.7 Hz), 115.41 (d, JCF = 20.8 Hz), 111.38 (d, JCF= 15.6 Hz), 94.41 (d, JCF = 3.4 Hz), 77.82 (d, JCF = 0.9 Hz), 68.58,67.97, 33.36, 25.42. HRMS (EI) ([M]+) calcd for C12H11FO:190.0794, found: 190.0798.

2-Methyl-2-(phenylethynyl)tetrahydrofuran (3o). Colorlessoil. 1H NMR (400 MHz, CDCl3) δ: 7.44–7.42 (m, 2H), 7.30–7.29(m, 3H), 4.06–3.95 (m, 2H), 2.34–2.28 (m, 1H), 2.20–2.12 (m,1H), 2.03–1.98 (m, 1H), 1.90–1.83 (m, 1H), 1.65 (s, 3H); 13CNMR (100 MHz, CDCl3) δ: 131.68, 128.18, 128.07, 123.01,92.36, 82.73, 76.40, 67.65, 40.18, 27.72, 25.72. HRMS (ESI)([M + H]+) calcd for C13H15O: 187.1123, found: 187.1124.

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2-Methyl-2-(p-tolylethynyl)tetrahydrofuran (3p). Colorlessoil. 1H NMR (400 MHz, CDCl3) δ: 7.32 (d, J = 7.6 Hz, 2H), 7.10(d, J = 7.6 Hz, 2H), 4.06–3.94 (m, 2H), 2.34 (s, 3H), 2.31–2.27(m, 1H), 2.22–2.11 (m, 1H), 2.05–1.95 (m, 1H), 1.90–1.83 (m,1H), 1.64 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 137.99, 131.46,128.82, 119.82, 91.48, 82.72, 76.32, 67.50, 40.08, 27.65, 25.61,21.32. HRMS (EI) ([M]+) calcd for C14H16O: 200.1201, found:200.1199.

2-((4-Chlorophenyl)ethynyl)-2-methyltetrahydrofuran (3q).Colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.34 (d, J = 8.0 Hz,2H), 7.26 (d, J = 8.0 Hz, 2H), 4.03–3.94 (m, 2H), 2.31–2.26 (m,1H), 2.18–2.09 (m, 1H), 2.03–1.97 (m, 1H), 1.90–1.83 (m, 1H),1.63 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 133.96, 132.80,128.39, 121.39, 93.28, 81.51, 76.23, 67.61, 39.99, 27.56, 25.62.HRMS (EI) ([M]+) calcd For C13H13ClO: 220.0655, found:220.0654.

2-(Phenylethynyl)tetrahydro-2H-pyran (3r).16 Colorless oil.1H NMR (400 MHz, CDCl3) δ: 7.48–7.46 (m, 2H), 7.32–7.27 (m,3H), 4.53–4.51 (m, 1H), 4.09–4.04 (m, 1H), 3.63–3.57 (m, 1H),1.95–1.87 (m, 2H), 1.84–1.77 (m, 1H), 1.65–1.57 (m, 3H); 13CNMR (100 MHz, CDCl3) δ: 131.76, 128.29, 128.22, 122.77,88.15, 85.19, 67.46, 66.64, 32.20, 25.69, 21.84.

2-(Phenylethynyl)-1,4-dioxane (3s).15a Colorless oil. 1H NMR(400 MHz, CDCl3) δ: 7.47–7.45 (m, 2H), 7.32–7.31 (m, 3H),4.59–4.57 (m, 1H), 3.96–3.92 (m, 2H), 3.78–3.68 (m, 4H); 13CNMR (100 MHz, CDCl3) δ: 131.87, 128.70, 128.27, 122.07,86.56, 84.32, 70.41, 66.46, 66.40, 65.80.

2-((4-(tert-Butyl)phenyl)ethynyl)-1,4-dioxane (3t). Colorlessoil. 1H NMR (400 MHz, CDCl3) δ: 7.40 (d, J = 8.0 Hz, 2H), 7.33(d, J = 8.4 Hz, 2H), 4.59–4.56 (m, 1H), 3.96–3.92 (m, 2H),3.79–3.67 (m, 4H), 1.31 (s, 9H); 13C NMR (100 MHz, CDCl3) δ:151.98, 131.60, 125.27, 119.01, 86.70, 83.59, 70.49, 66.55,66.38, 65.84, 34.78, 31.13. HRMS (EI) ([M]+) calcd forC16H20O2: 244.1463, found: 244.1468.

1-(4-((2,3-Dihydrobenzofuran-2-yl)ethynyl)phenyl)ethanone(3u). Colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.90 (d, J =8.4 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 7.2 Hz, 1H),7.23–7.19 (m, 1H), 6.98–6.95 (m, 1H), 6.87 (d, J = 8.0 Hz, 1H),4.87–4.83 (m, 1H), 4.65–4.61 (m, 1H), 4.56–4.52 (m, 1H), 2.60(s, 3H); 13C NMR (100 MHz, CDCl3) δ: 197.16, 159.33, 136.15,

131.74, 129.04, 128.07, 127.79, 126.85, 124.63, 121.08, 109.99,91.35, 82.05, 76.22, 34.48, 26.47. HRMS (EI) ([M]+) calcd forC18H14O2: 262.0994, found: 262.0999.

1-(4-((1,3-Dihydroisobenzofuran-1-yl)ethynyl)phenyl)etha-none (3v). Colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.89 (d,J = 8.0 Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H), 7.45–7.43 (m, 1H),7.37–7.35 (m, 2H), 7.29–7.27 (m, 1H), 6.14 (s, 1H), 5.31–5.28(m, 1H), 5.16–5.13 (m, 1H), 2.59 (s, 3H); 13C NMR (100 MHz,CDCl3) δ: 197.16, 138.74, 138.60, 136.39, 131.85, 128.24,128.02, 127.78, 127.22, 121.75, 121.06, 90.39, 85.10, 73.69,72.91, 26.48. HRMS (EI) ([M]+) calcd For C18H14O2: 262.0994,found: 262.0993.

(3,4-Dimethoxybut-1-yn-1-yl)benzene (3w). Colorless oil. 1HNMR (400 MHz, CDCl3) δ: 7.47–7.45 (m, 2H), 7.33–7.32 (m,3H), 4.45–4.41 (m, 1H), 3.69–3.66 (m, 2H), 3.54 (s, 3H), 3.47 (s,3H); 13C NMR (100 MHz, CDCl3) δ: 131.82, 128.56, 128.28,122.34, 86.85, 84.86, 74.92, 71.07, 59.37, 56.89. HRMS (ESI)([M + H]+) calcd for C12H15O2: 191.1072, found: 191.1075.

1-((Tetrahydrofuran-2-yl)ethynyl)cyclohexanol (3x).22 Color-less oil. 1H NMR (400 MHz, CDCl3) δ: 4.63–4.61 (m, 1H),3.97–3.92 (m, 1H), 3.83–3.80 (m, 1H), 2.27 (br, s, 1H),2.17–2.15 (m, 1H), 2.05–1.88 (m, 5H), 1.68–1.66 (m, 2H),1.58–1.50 (m, 4H), 1.24–1.21 (m, 2H); 13C NMR (100 MHz,CDCl3): δ: 88.04, 83.90, 68.42, 68.03, 67.64, 39.74, 33.32, 25.21,25.04, 23.21.

2-(Hept-1-yn-1-yl)tetrahydrofuran (3y).23 Colorless oil. 1HNMR (400 MHz, CDCl3) δ: 4.57–4.55 (m, 1H), 3.98–3.93 (m,1H), 3.82–3.76 (m, 1H), 2.21 (t, J = 7.0 Hz, 2H), 2.15–2.08 (m,1H), 2.04–2.00 (m, 1H), 1.96–1.87 (m, 2H), 1.54–1.47 (m, 2H),1.33–1.26 (m, 4H), 0.90 (t, J = 6.4 Hz, 3H); 13C NMR (100 MHz,CDCl3): δ: 85.21, 79.74, 68.33, 67.56, 33.42, 30.94, 28.23, 25.31,22.09, 18.63, 13.88.

2-(Phenylethynyl)-1,3-dioxolane (3z).24 Colorless oil. 1HNMR (400 MHz, CDCl3) δ: 7.48–7.46 (m, 2H), 7.36–7.32 (m,3H), 5.90 (s, 1H), 4.17–4.13 (m, 2H), 4.01–3.98 (m, 2H); 13C

Organic & Biomolecular Chemistry Paper

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NMR (100 MHz, CDCl3) δ: 131.94, 128.99, 128.31, 121.60,93.45, 85.21, 84.45, 64.61.

4-(Phenylethynyl)-1,3-dioxolane (3z′). Colorless oil. 1H NMR(400 MHz, CDCl3) δ: 7.47–7.45 (m, 2H), 7.34–7.32 (m, 3H), 5.11(s, 1H), 5.08 (s, 1H), 4.95 (t, J = 6.0 Hz, 1H), 4.21–4.18 (m, 1H),3.95–3.92 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 131.81,128.73, 128.29, 122.08, 95.20, 86.22, 85.65, 70.59, 65.81. HRMS(EI) ([M]+) calcd for C11H10O2: 174.0681, found: 174.0677.

(E)-2-Styryl-tetrahydrofuran (E-5a).12 Colorless oil. 1H NMR(400 MHz, CDCl3) δ: 7.41–7.39 (m, 2H), 7.33–7.30 (m, 2H),7.27–7.22 (m, 1H), 6.61 (d, J = 16.0 Hz, 1H), 6.23 (dd, J = 16.0,6.0 Hz, 1H), 4.52–4.47 (m, 1H), 4.02–3.97 (m, 1H), 3.89–3.83(m, 1H), 2.18–2.10 (m, 1H), 2.03–1.94 (m, 2H), 1.77–1.71 (m,1H); 13C NMR (100 MHz, CDCl3) δ: 136.76, 130.43, 130.32,128.40, 127.39, 126.36, 79.56, 68.08, 32.30, 25.82.

(E)-2-Methyl-2-styryl-tetrahydrofuran (E-5b). Colorless oil.1H NMR (400 MHz, CDCl3) δ: 7.41–7.39 (m, 2H), 7.34–7.30 (m,2H), 7.25–7.21 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.26 (d, J =16.0 Hz, 1H), 3.97–3.94 (m, 2H), 2.03–1.96 (m, 3H), 1.83–1.76(m, 1H), 1.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 137.10,135.43, 128.38, 127.08, 126.69, 126.27, 82.29, 67.54, 37.76,26.68, 25.63. HRMS (EI) ([M]+) calcd For C13H16O: 188.1201,found: 188.1202.

(Z)-4-((1-Phenyl-2-(tetrahydrofuran-2-yl)vinyl)oxy)benzonitrile(5c). White solid. 1H NMR (400 MHz, CDCl3) δ: 7.52–7.50 (m,2H), 7.30–7.27 (m, 3H), 7.25–7.21 (m, 2H), 6.99–6.93 (m, 3H),5.92 (d, J = 8.0 Hz, 1H), 4.80–4.74 (m, 1H), 3.97–3.92 (m, 1H),3.80–3.75 (m, 1H), 2.12–2.07 (m, 1H), 2.01–1.87 (m, 2H),1.72–1.67 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 157.11,149.90, 134.59, 129.41, 128.33, 125.71, 121.59, 118.83, 115.70,74.04, 67.82, 32.33, 26.04. HRMS (ESI) ([M + H]+) calcd forC18H19O2: 267.1385, found: 267.2382.

(Z)-4-((1-Phenyl-2-(tetrahydrofuran-2-yl)vinyl)oxy)benzonitrile(5d). White solid. 1H NMR (400 MHz, CDCl3) δ: 7.54 (d, J =8.0 Hz, 2H), 7.46–7.45 (m, 2H), 7.31–7.27 (m, 3H), 7.05 (d, J =8.0 Hz, 2H), 5.98 (d, J = 8.0 Hz, 1H), 4.70–4.65 (m, 1H),3.96–3.91 (m, 1H), 3.80–3.74 (m, 1H), 2.11–2.05 (m, 1H),

2.02–1.96 (m, 1H), 1.94–1.89 (m, 1H), 1.72–1.63 (m, 1H); 13CNMR (100 MHz, CDCl3) δ: 160.49, 149.13, 134.03, 133.49,128.87, 128.62, 125.43, 119.62, 118.70, 116.49, 105.27, 73.67,67.94, 32.33, 26.03. HRMS (ESI) ([M + H]+) calcd ForC19H18NO2: 292.1338, found: 292.1338.

(E/Z)-(2-Bromovinyl)benzene (E-4a and Z-4a) [E/Z = 5/1]. 1HNMR (400 MHz, CDCl3) δ: 7.45–7.39 (m, 1H), 7.37–7.34 (m,5H), 7.15 (d, J = 14.0 Hz, 1H), 7.11 (d, J = 8.4 Hz, 0.2H), 6.81 (d,J = 14.0 Hz, 1H), 6.48 (d, J = 8.4 Hz, 0.2H).

(E/Z)-2-Styryltetrahydrofuran (E-5a and Z-5a) [E/Z =5/1].12 1H NMR (400 MHz, CDCl3) δ: 7.40–7.38 (m, 2H),7.35–7.30 (m, 2.8H), 7.28–7.22 (m, 1.2H), 6.61 (d, J = 11.6 Hz,0.2H), 6.60 (d, J = 15.6 Hz, 1H), 6.22 (dd, J = 16.0, 6.4 Hz, 1H),5.72 (dd, J = 11.6, 8.8 Hz, 0.2H), 4.71–4.65 (m, 0.2H), 4.52–4.47(m, 1H), 4.01–3.96 (m, 1.2H), 3.88–3.79 (m, 1.2H), 2.17–2.12(m, 1.2H), 2.03–1.94 (m, 2.4H), 1.75–1.71 (m, 1.2H).

(E/Z)-2-Methyl-2-styryltetrahydrofuran (E-5b and Z-5b) [E/Z =5/1]. 1H NMR (400 MHz, CDCl3) δ: 7.40–7.38 (m, 2.4H),7.33–7.29 (m, 2.6H), 7.24–7.21 (m, 1H), 6.61 (d, J = 8.4 Hz,0.2H), 6.56 (d, J = 16.0 Hz, 1H), 6.61 (d, J = 16.0 Hz, 1H), 6.20(d, J = 7.2 Hz, 0.2H), 4.26–4.21 (m, 0.2H), 3.97–3.94 (m, 2H),2.01–1.80 (m, 4.8H), 1.62 (s, 0.6H), 1.42 (s, 3H).

Acknowledgements

This work was financially supported by the National ScienceFoundation of China (no. 21172092 and 21372095).

Notes and references

1 For recent reviews on C–H activation, see: (a) G. Song,F. Wang and X. Li, Chem. Soc. Rev., 2012, 41, 3651;(b) Z. Shi, C. Zhang, C. Tang and N. Jiao, Chem. Soc. Rev.,2012, 41, 3381; (c) F. W. Patureau, J. Wencel-Delord andF. Glorius, Aldrichimica Acta, 2012, 45, 31; (d) N. Kuhl,M. N. Hopkinson, J. Wencel-Delord and F. Glorius, Angew.Chem., Int. Ed., 2012, 51, 10236; (e) C.-L. Sun, B.-J. Li andZ.-J. Shi, Chem. Rev., 2011, 111, 1293; (f ) C. S. Yeung andV. M. Dong, Chem. Rev., 2011, 111, 1215; (g) S. H. Cho,J. Y. Kim, J. Kwak and S. Chang, Chem. Soc. Rev., 2011, 40,

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5068; (h) J. Bras and J. Muzart, Chem. Rev., 2011, 111, 1170;(i) D. A. Colby, R. G. Bergman and J. A. Ellman, Chem. Rev.,2010, 110, 624; ( j) T. W. Lyons and M. S. Sanford, Chem.Rev., 2010, 110, 1147; (k) O. Daugulis, H.-Q. Do andD. Shabashov, Acc. Chem. Res., 2009, 42, 1074; (l) R. Giri,B.-F. Shi, K. M. Engle, N. Maugel and J.-Q. Yu, Chem. Soc.Rev., 2009, 38, 3242.

2 (a) S. Yanagisawa, K. Ueda, T. Taniguchi and K. Itami, Org.Lett., 2008, 10, 4673; (b) W. Liu, H. Cao, H. Zhang,H. Zhang, K. H. Chung, C. He, H. Wang, F. Y. Kwong andA. Lei, J. Am. Chem. Soc., 2010, 132, 16737; (c) C.-L. Sun,H. Li, D.-G. Yu, M. Yu, X. Zhou, X.-Y. Lu, K. Huang,S.-F. Zheng, B.-J. Li and Z.-J. Shi, Nat. Chem., 2010, 2, 1044;(d) E. Shirakawa, K.-i. Itoh, T. Higashino and T. Hayashi,J. Am. Chem. Soc., 2010, 132, 15537.

3 (a) D. P. Curran, Nat. Chem., 2012, 4, 958; (b) A. Studer andD. P. Curran, Angew. Chem., Int. Ed., 2011, 50, 5018.

4 For selected examples, see: (a) Z. Shi and F. Glorius, Chem.Sci., 2013, 4, 829; (b) H. Zhang, R. Shi, A. Ding, L. Lu,B. Chen and A. Lei, Angew. Chem., Int. Ed., 2012, 51, 12542;(c) E. Shirakawa, Y. Hayashi, K.-i. Itoh, R. Watabe,N. Uchiyama, W. Konagaya, S. Masui and T. Hayashi,Angew. Chem., Int. Ed., 2012, 51, 218; (d) D. P. Hari,P. Schroll and B. KÖnig, J. Am. Chem. Soc., 2012, 134, 2958;(e) H. Li, L. Wang, Y. Zhang and J. Wang, Angew. Chem., Int.Ed., 2012, 51, 2943; (f ) M. C. Pérez-Aguilar and C. Valdés,Angew. Chem., Int. Ed., 2012, 51, 5953; (g) A. Kirste,B. Elsler, G. Schnakenburg and S. R. Waldvogel, J. Am.Chem. Soc., 2012, 134, 3571; (h) T. Morofuji, A. Shimizu andJ.-i. Yoshida, Angew. Chem., Int. Ed., 2012, 51, 7259;(i) J. A. Souto, P. Becker, Á. Iglesias and K. Muñiz, J. Am.Chem. Soc., 2012, 134, 15505; ( j) C. Chen, L. Chu andF.-L. Qing, J. Am. Chem. Soc., 2012, 134, 12454;(k) E. Shirakawa, X. Zhang and T. Hayashi, Angew. Chem.,Int. Ed., 2011, 50, 4671; (l) T. Truong and O. Daugulis,J. Am. Chem. Soc., 2011, 133, 4243; (m) A. P. Antonchick,R. Samanta, K. Kulikov and J. Lategahn, Angew. Chem., Int.Ed., 2011, 50, 8605; (n) A. A. Kantak, S. Potavathri,R. A. Barham, K. M. Romano and B. DeBoef, J. Am. Chem.Soc., 2011, 133, 19960; (o) H. J. Kim, J. Kim, S. H. Cho andS. Chang, J. Am. Chem. Soc., 2011, 133, 16382;(p) B. S. Bhakuni, A. Kumar, S. J. Balkrishna, J. A. Sheikh,S. Konar and S. Kumar, Org. Lett., 2012, 14, 2838; (q) S. De,S. Ghosh, S. Bhunia, J. A. Sheikh and A. Bisai, Org. Lett.,2012, 14, 4466; (r) Y. Wu, S. M. Wong, F. Mao, T. L. Chan andF. Y. Kwong, Org. Lett., 2012, 14, 5306; (s) C.-L. Sun, Y.-F. Gu,B. Wang and Z.-J. Shi, Chem.–Eur. J., 2011, 17, 10844;(t) Y. Qiu, Y. Liu, K. Yang, W. Hong, Z. Li, Z. Wang, Z. Yaoand S. Jiang, Org. Lett., 2011, 13, 3556; (u) D. S. Roman,Y. Takahashi and A. B. Charette, Org. Lett., 2011, 13, 3242;(v) W.-C. Chen, Y.-C. Hsu, W.-C. Shih, C.-Y. Lee,W.-H. Chuang, Y.-F. Tsai, P. P.-Y. Chen and T.-G. Ong, Chem.Commun., 2012, 48, 6702; (w) M. Brasse, J. A. Ellman andR. G. Bergman, Chem. Commun., 2011, 47, 5019.

5 (a) I. Vilotijevic and T. F. Jamison, Angew. Chem., Int. Ed.,2009, 48, 5250; (b) B. Figadere, G. Jalce and X. Franck,

Tetrahedron: Asymmetry, 2009, 20, 2537; (c) I. Larrosa,P. Romea and F. Urpì, Tetrahedron, 2008, 64, 2683;(d) J. P. Wolfe and M. B. Hay, Tetrahedron, 2007, 63, 261;(e) P. A. Clarke and S. Santos, Eur. J. Org. Chem., 2006,2045; (f ) K. S. Yeung and I. Paterson, Chem. Rev., 2005, 105,4237; (g) T. Nakata, Chem. Rev., 2005, 105, 4314;(h) J. Muzart, Tetrahedron, 2005, 61, 5955; (i) A. Bermejo,B. Figadere, M. C. Zafra-Polo, I. Barrachina, E. Estornelland D. Cortes, Nat. Prod. Rep., 2005, 22, 269;( j) C. J. Dutton, B. J. Banks and C. B. Cooper, Nat. Prod.Rep., 1995, 12, 165.

6 S.-Y. Zhang, F.-M. Zhang and Y.-Q. Tu, Chem. Soc. Rev.,2011, 40, 1937.

7 D. Liu, C. Liu, H. Li and A. Lei, Angew. Chem., Int. Ed.,2013, 52, 4453.

8 Z. Li, R. Yu and H. Li, Angew. Chem., Int. Ed., 2008, 47, 7497.9 (a) M. M. Díaz-Requejo, T. R. Belderraín, M. C. Nicasio,

S. Trofimenko and P. J. Pérez, J. Am. Chem. Soc., 2002, 124,896; (b) J. M. Fraile, J. I. García, J. A. Mayoral andM. Roldán, Org. Lett., 2007, 9, 731; (c) H. M. L. Davies,T. Hansen and M. R. Churchill, J. Am. Chem. Soc., 2000,122, 3063; (d) H. M. L. Davies and T. Hansen, J. Am. Chem.Soc., 1997, 119, 9075; (e) H. Suematsu and T. Katsuki, J. Am.Chem. Soc., 2009, 131, 14218.

10 R. Baati, A. Valleix, C. Mioskowski, D. K. Barma andJ. R. Falck, Org. Lett., 2000, 2, 485.

11 J. Xiang, W. Jiang, J. Gong and P. L. Fuchs, J. Am. Chem.Soc., 1997, 119, 4123.

12 Z.-Q. Liu, L. Sun, J.-G. Wang, J. Han, Y.-K. Zhao andB. Zhou, Org. Lett., 2009, 11, 1437.

13 (a) T. Yoshimitsu, T. Makino and H. Nagaoka, J. Org.Chem., 2003, 68, 7548; (b) T. Yoshimitsu, Y. Arano andH. Nagaoka, J. Org. Chem., 2003, 68, 625; (c) K.-i. Yamada,Y. Yamamoto and K. Tomioka, Org. Lett., 2003, 5, 1797.

14 D. S. Brown and S. V. Ley, Tetrahedron Lett., 1988, 29, 4869.15 (a) J. Gong and P. L. Fuchs, J. Am. Chem. Soc., 1996, 118,

4486; (b) J. Xiang and P. L. Fuchs, J. Am. Chem. Soc., 1996,118, 11986 The important expansion of Inoue usingirradiation conditions with more practical alkynyl sulfones,see: (c) T. Hoshikawa, S. Kamijo and M. Inoue, Org. Biomol.Chem., 2013, 11, 164.

16 D. S. B. Daniels, A. L. Thompson and E. A. Anderson,Angew. Chem., Int. Ed., 2011, 50, 11506.

17 (a) T. He, L. Yu, L. Zhang, L. Wang and M. Wang, Org. Lett.,2011, 13, 5016. Selected papers for the sp–sp3 bonds for-mation, see: (b) O. Vechorkin, A. Godinat, R. Scopelliti andX. Hu, Angew. Chem., Int. Ed., 2011, 50, 11777; (c) J. Yi,X. Lu, Y.-Y. Sun, B. Xiao and L. Liu, Angew. Chem., Int. Ed.,2013, 52, 12409; (d) X. Liu, Z. Wang, X. Cheng and C. Li,J. Am. Chem. Soc., 2012, 134, 14330; (e) Y. Fukumoto,M. Hagihara, F. Kinashi and N. Chatani, J. Am. Chem. Soc.,2011, 133, 10014; (f ) G. Altenhoff, S. Würtz and F. Glorius,Tetrahedron Lett., 2006, 47, 2925.

18 (a) S. Wang, P. Li, L. Yu and L. Wang, Org. Lett., 2011, 13,5968; (b) A. Wagner, M. P. Heitz and C. Mioskowski, Tetra-hedron Lett., 1990, 31, 3141.

Organic & Biomolecular Chemistry Paper

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19 For the preparation of vinyl cycloethers, also see:(a) Y.-J. Jang, Y.-K. Shih, J.-Y. Liu, W.-Y. Kuo and C.-F. Yao,Chem.–Eur. J., 2003, 9, 2123; (b) Y. Zhang and C.-J. Li, Tetra-hedron Lett., 2004, 45, 7581; (c) Z. Chen, Y.-X. Zhang, Y. An,X.-L. Song, Y.-H. Wang, L.-L. Zhu and L. Guo, Eur. J. Org.Chem., 2009, 5146.

20 X-ray single crystal structure of 5d, which is numberedCCDC 955471 at The Cambridge Crystallographic DataCentre.

.

21 KOAc (99.96%) was purchased from Aladdin Co. The reac-tion solution was analysed by ICP-MS, and the determi-nation data indicated that Cu, Pd, Ni, Fe, Co, Ru, and Rhare less than 0.2 ppm (under detection limits).

22 During revision of this manuscript, a similar work wasreported using NaF by Liang, and see: Y. Yang, H. Huang,X. Zhang, W. Zeng and Y. Liang, Synthesis, 2013, 3137–3146for detail.

23 L. Crombie and L. J. Rainbow, J. Chem. Soc., Perkin Trans. 1,1994, 673–688.

24 A. R. Katritzky, H. H. Odens and M. V. Voronkov, J. Org.Chem., 2000, 65, 1886.

Paper Organic & Biomolecular Chemistry

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